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Animal Models of Addiction

成瘾动物模型

基本信息

批准号：
10740648
负责人：
Carrie Ferrario
金额：
$ 45.6万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10740648
关键词：
AMPA Receptors Animal Model Behavior Behavioral Biochemical Biological Brain Calcium Cocaine Consumption Corpus striatum structure Cues Data Development Dialysis procedure Dopamine Drug usage Electrophysiology (science)Excision Female Food Glutamates Goals Hyperactivity Incentives Incubated Intake Kava Literature Mediating Methods Modeling Motivation Neurobiology Nucleus Accumbens Outcome Pattern Permeability Pharmaceutical Preparations Preparation Procedures Psychology Rattus Reporting Rodent Sampling Self Administration System Testing Therapeutic Time Withdrawal addiction behavioral economics cocaine craving cocaine seeking cocaine self-administration cocaine use data integration dopamine system drug abuse prevention drug seeking behavior economic indicator experience experimental study indexing male neural neuroadaptation neurotransmission preclinical study psychologic response therapeutic development transmission process

项目摘要

Abstract: It is generally accepted that limited (Short Access, ShA) cocaine self-administration experience does not produce changes in brain and behavior associated with addiction. The most widely used models of addiction involve Long Access procedures (LgA, 6hrs+/day), which greatly increase the amount of drug consumption. LgA produces a number of addiction-like behaviors, and changes in brain, not seen with ShA. However, in addition to the amount of cocaine use, the temporal pattern of use – how intermittent it is – is also important in producing addiction-like behavior and associated neuroadaptations. Zimmer et al. (2013) developed an intermittent access self-administration procedure (IntA) to better model the intermittent patterns of cocaine use seen in addicts. He found that, despite much less total drug consumption, motivation for cocaine was higher in rats with prior IntA experience than those with LgA experience. Consistent with this, we found that IntA produces robust incentive-sensitization, as indicated by a progressive increase in cocaine demand (based on behavioral economic indicators), an associated escalation of intake, and very robust reinstatement of cocaine seeking behavior – despite consuming much less drug than under LgA conditions. Thus, our Overall Aim is to directly compare and contrast the behavioral, psychological and neurobiological effects of these two models of addiction. The overall goal is to determine whether the changes in brain and behavior produced by LgA vs. IntA experience only differ quantitatively, or, whether there are qualitative differences in outcomes. This information will be critical in making informed decisions about the animal model to use in preclinical studies of addiction, and will also be important in determining directions in the development of therapeutics.

摘要：人们普遍认为，有限的（短期接触，ShA）可卡因自我管理经验不会产生与成瘾相关的大脑和行为变化。最广泛使用的成瘾模型涉及长期访问程序（LGA，6小时+/天），这大大增加了毒品消费量。LgA产生许多成瘾样行为，脑内变化，ShA未见。然而，除了可卡因的使用量，使用的时间模式--它的间歇性--在产生类似成瘾的情况下也很重要行为和相关的神经适应。Zimmer等人（2013）开发了一种间歇性访问自我管理程序（IntA），以更好地模拟可卡因的间歇模式在瘾君子中使用。他发现，尽管总的药物消费量少得多，可卡因在有IntA经验的大鼠中高于有LgA经验的大鼠。一致有了这个，我们发现IntA产生了强大的激励敏感化，如图所示。可卡因需求逐步增加（根据行为经济指标），相关的摄入量增加，以及可卡因寻求行为的强烈恢复- 尽管消耗的药物比在LGA条件下少得多。因此，我们的总体目标是直接比较和对比这两种行为，心理和神经生物学影响成瘾的模型总体目标是确定大脑和行为的变化是否由LgA与IntA经验产生的差异只是数量上的，或者，是否有质量上的差异，结果的差异。这一信息对于作出有关动物模型用于成瘾的临床前研究，也将是重要的，治疗学的发展方向。